Calvin Zabo was born in Trenton, New Jersey. He was a morally abject but brilliant biochemist who was fascinated by the effect of hormones on human physiology. One of his favorite stories was Stevenson's 1886 classic, Strange Case of Dr Jekyll and Mr Hyde. He was convinced that the experiment Dr. Jekyll performed in the story could actually be accomplished, and became obsessed with the idea of unleashing his full bestial nature in a superhuman form. However, he needed money to do this, so he robbed his various employers systematically. Though too intelligent to be caught, the medical community was suspicious of his tendency to always be employed by organizations which were subsequently robbed. Zabo eventually sought work as a surgeon in a hospital where Donald Blake was a directing physician, yet Blake would not allow him a job due to his history. Zabo was enraged that Blake would not give him the position, even though he did indeed intend to rob the organization, and swore revenge. He was eventually successful in creating his formula, and turned into a huge, Hulk-like creature he called "Mister Hyde," named after the character in the novel. In this new form, he found he had superhuman strength enabling him to crush cars and tear through steel as though it were made of cardboard. With his new superhuman powers he sought out Blake, whom he tried to kill by throwing him from a window, but Blake transformed into Thor by striking his cane on the wall and survived, claiming he had saved Blake. Hyde, hearing of this on the radio, decided to eliminate Thor, and tried to frame him for a bank robbery by using his superhuman strength to tear open a bank vault while disguised as Thor. While Donald and Jane were out, Mister Hyde met and kidnapped them at gunpoint. As Don Blake, Thor was tied up next to a bomb that would explode in 24 hours unless Mr. Hyde defused it. However, when attempting to steal a Polaris submarine to roam the seas like a pirate, Hyde was defeated and the authorities, seeing his superhuman strength, realized he must have impersonated Thor, but Thor was forced to allow him to escape, as Jane Foster thought Blake was still in danger.[1]

Hyde went into business as a full-time professional super-criminal and partnered himself with the Cobra to get revenge upon Thor, but they were both defeated despite getting Thor's hammer from him briefly.[2] With the Cobra, he was bailed out and employed by Loki to kidnap Jane Foster, and they battled Thor again. Loki doubled their powers to try to help them. Loki showed Thor where Jane Foster was being held. The house had many traps set up for Thor, and Jane Foster was almost killed in an explosion. Thor was able to defeat both villains, and Mister Hyde was caught by a ray which paralyzed him. Both Hyde and Cobra were jailed, and Jane's life was saved by an Asgardian formula Balder sent to Thor.[3] Hyde and the Cobra escaped prison, but were eventually recaptured by Daredevil.[4] They teamed with the Jester to get revenge, but were defeated again.[5] With the Scorpion, Hyde then battled Captain America and the Falcon.[6] Teaming with the Cobra again, Hyde attempted to acquire Cagliostro's serum.[7] While serving in prison following this failed attempt, Hyde was ensnared by the mind-control power of the Purple Man, and forced to battle Daredevil in an arena alongside Cobra, the Jester, and the Gladiator.[8]

Tiring of their repeated failures, the Cobra elected to sever their partnership when he escaped from Ryker's Island, taking the time to taunt Hyde before leaving.[9] Hyde has never forgiven him for the slight. With Batroc, Hyde later blackmailed New York City with a hijacked supertanker and attempted to destroy the entire city in order to kill Cobra. Eventually, he was defeated by Captain America with Batroc's aid.[10] Hyde again stalked Cobra seeking revenge, and this time battled Spider-Man.[11] He was imprisoned again, but escaped Ryker's Island and battled Spider-Man and the Black Cat during another attempt at Cobra's life.[12] Hyde later battled Daredevil again.[13]

Hyde later fought with the Grey Hulk and received head trauma that limited his ability to transform.[18] He was subsequently caught by the police when he coincidentally checked into the same hotel as the one where the Daily Bugle staff were attending Robbie Robertson's retirement party, allowing Peter Parker to defeat him using an improvised costume.[19] Shortly after, Hyde had several run-ins with the Ghost Rider in which he was defeated with the Penance Stare.[20]

Hyde briefly helped the symbiote-bonded Toxin track Cobra after a prison escape by providing a piece of skin for the symbiote to track.[21]

Zabo was being held in The Raft (the Ryker's Island Prison complex) 6 months after the events of Avengers Disassembled.[22] When a prison break was caused by the villain Electro, Zabo emerged in his Hyde persona, fought with Daredevil, and was knocked unconscious by Luke Cage.[23]

Zabo grafts abilities similar to the powers of Spider-Man to homeless teenagers. After Spider-Man revealed his identity during the Civil War storyline, Zabo sought to recreate the circumstances of Spider-Man's "birth", by taking in orphans off the street, imbuing them with spider-powers, and seeing whether or not the teenagers would give in to their darker impulses. During the ensuing battle with Spider-Man, Hyde pulled webbing off his face, taking his eyelids with it, and was hit in the face with hydrochloric acid, courtesy of one of his own guinea pigs. It is stated by Spider-Man that he has been left blinded and had his face ruined as a result. Dr. Curt Connors was later seen aiding Spider-Man in a cure for Calvin, one of Zabo's test subjects.[25]

Hyde's daughter is Daisy Johnson, who is a member of S.H.I.E.L.D.; her mother was apparently a prostitute with whom Calvin Zabo regularly had 'business',[26] and the girl was put up for adoption after birth. Daisy subsequently manifested superpowers inherited from Zabo's mutated genetic code.

Later he was seen along with Firebrand, King Cobra, and Mauler, who attacked Yellowjacket, Constrictor and other Initiative staff and trainees.[28]

Mister Hyde worked with Boomerang, Tiger Shark, and Whirlwind to manipulate Venom III into procuring Norman Osborn's fortunes. This was thwarted by Venom and Green Goblin as Norman threw a bomb into Mister Hyde's mouth causing him to spit out blood. Norman Osborn then warned Mister Hyde and the villains that if they cross him again, he will kill everyone that they ever loved before they are tortured to death.[29]

Later, Mister Hyde began a drug operation in California where he came into conflict with Robbie Reyes after his car had some of Mister Hyde's pills inside. Mister Hyde's mercenaries chase Robbie down during the race in order to retrieve the car and the pills. Robbie is gunned down by the mercenaries when he mistakes them for police, and they torch the scene. Robbie is revived as a demonic being called the Ghost Rider who sports a flaming helmet-like head. In this form, Robbie drives off in the car, now similarly ablaze. The Ghost Rider defeats a few mercenaries and soon disappears in an explosion.[33] Robbie eventually fights and defeats Zabo, becoming something of a local hero and urban legend.[34] Having regrouped and refined his Hyde Formula into new blue pills, Calvin Zabo gradually takes over the L.A. criminal underground with his "Blue Hyde Brigade," which includes Guero and his gang, longtime enemies of Robbie, calling themselves the "Blue Krüe."[35]

During the Avengers: Standoff! storyline, Mister Hyde was an inmate of Pleasant Hill, a gated community established by S.H.I.E.L.D.[36][37]

The process that transforms Dr. Calvin Zabo into his Mr. Hyde persona is a hormonal transformation caused by ingestion of chemical formula.[38] As his body adjusted to its new form, Mr. Hyde's strength, stamina, durability, and resistance to physical injury all increase to superhuman levels. Hyde's powers are sufficient to stand toe to toe with the likes of Thor and survive. He has been shown tearing apart steel in a bank vault with ease.[39] Through further experimental procedures over the years, his strength has been increased beyond its original limits. Mr. Hyde must ingest his special chemical formula periodically to maintain his ability to transform himself from one identity to the other at will; mental fatigue or injury can impair his ability to transform himself into Mr. Hyde. He employs a device that resembles a wristwatch that contains a supply of the formula that he can use to deliver it directly into his bloodstream, enabling him to transform at the push of a button.

In the timeline of the "Age of Apocalypse" storyline Mr. Hyde (as well as the Cobra) is a near-feral and cannibal "Scavenger". He is known to prowl graveyards and attack anyone entering his territory.[40]

Mr. Hyde appeared in the ElseworldsDaredevil/Batman: Eye for an Eye crossover book. Two-Face partnered with Mister Hyde for a series of technological robberies. In truth, Two-Face had implanted Hyde's brain with the material needed to "grow" an experimental "organic" computer chip, and fed Hyde pills to keep him enraged. Once grown, the chip would kill Hyde, its current growth also weakening Hyde's strength as his energy is diverted to support the chip (Batman noting during the fight that Hyde should normally have a punch that could knock Superman into orbit). Hyde berates Two-Face, proud he has abandoned his past as Zabo and insults Two-Face for hanging onto his Harvey Dent side, as well as using a coin to decide between right and wrong. Two-Face is glad the process will kill Hyde. In the end, Daredevil uses his past friendship with Dent to talk Two-Face into supplying the antidote for the chip, which saves Hyde's life.[41]

A zombified Mister Hyde appears in Marvel Zombies 4. He is seen attacking the new Midnight Sons, trying to bite one of them, but he is quickly killed by Man-Thing when he rips zombie Mister Hyde apart and holding a huge boulder and dropping it down on him, crushing the zombie Mister Hyde to death instantly.[45]

Mr. Hyde is the antagonist of the first two issues of this alternate universe retelling of Thor's origin. Thor, confused and partially amnesiac, stops Hyde from hassling an innocent woman. This drives Hyde into an obsession with Thor's new friend, a museum employee named Jane Foster.[46]

Calvin Zabo appears in the television series Agents of S.H.I.E.L.D., set in the Marvel Cinematic Universe, portrayed by Kyle MacLachlan. The character is initially known as "The Doctor" before being revealed to be named Calvin in the episode "What They Become".[47][48] The formula Cal takes is composed of, among other substances, anabolic-androgenic steroids, a liver enzyme blocker, various metabolic enhancers, methamphetamines, what appears to be gorilla testosterone, and a drop of peppermint. However, the formula requires at least one milligram of adrenaline to achieve its full effect. He is Daisy "Skye" Johnson's (portrayed by Chloe Bennet) father with "Johnson" being his original last name until he changed it for personal reasons while his wife is the ageless Inhuman named Jiaying (portrayed by Dichen Lachman). In the episode "S.O.S", Cal uses his formula to rampage on the S.H.I.E.L.D. headquarters before realizing that his wife's war against S.H.I.E.L.D. is a mistake. During the fight against Jiaying, Calvin saves Daisy by killing Jiaying. Later on, his memory is altered which allows him to start over with a new identity.

Mister Hyde appears in Marvel Heroes. He appears as the end boss in the Bronx Zoo One-Shot. During this one-shot, Calvin Zabo is broken out of prison by Lizard so that they can make their way to Lizard's hidden lab as part of Lizard's plot to have Calvin Zabo work on keeping his Curt Connors' side dormant. Once Calvin Zabo becomes Mister Hyde, he injects Lizard with his Hyde serum turning him into a more powerful version of himself as Mister Hyde plans to use his Lizard Serum/Hyde Serum to add to the Bronx Zoo's water supply resulting in lizard-like hybrids like Lizard-Monkeys, Lizard-Bears, Lizard-Bats, Lizard-Giraffes, and Lizard-Sharks. The players are able to fight their way past the lizard-like hybrids and defeat Mister Hyde. Mister Hyde later appears as a boss in Industry City Patrol.